The human epidermis is a multilayered, cohesive tissue with a unique functional architecture and it forms the primary barrier to the outside environment. Keratinocytes are the main component of the epidermis and their cohesion is essential in order to assure cell renewal and differentiation. The epidermal cells are linked one to another by special constructions named “junctions”. Different types of junctions exist, with different roles, such as rigidity (anchoring junctions), water resistance (tight junctions) and cell communication (gap junctions). Gap junctions are clusters of intercellular channels that allow the exchange by diffusion of ions (Ca2+, Mg2+) and small metabolites (glucose), nutrients, and signaling molecules (cyclic adenosine monophosphate, cAMP, or cyclic guanosine monophosphate cGMP) of less than 1 kDa between adjacent cells. This direct cytoplasmic exchange of metabolites and ions is thought to coordinate the epidermal homeostasis. Gap Junction-mediated Intercellular Communication (GJIC) is important in different physiological processes including cell differentiation, proliferation and electrical transmission, and it contributes to intracellular signaling, too [Scott C A, et al., “Connexins in epidermal homeostasis and skin disease”, Biochim. Biophys. Acta., 2012, August; 1818 (8): 1952-61]. This mechanism is strictly regulated and abnormal GJIC can result in several pathological disorders.
Gap junction channels consists of integral membrane proteins called connexins (Cx). Based on sequence similarities, connexins have been categorized into 2 phylogenetic groups, α and β, and they are named according to their molecular mass. The oligomerization of six connexin proteins forms a hemichannel, also named connexon. This connexon can be formed either from a single type of connexin (homomeric) or from more than one type (heteromeric). In addition, gap junctions may be homotypic, when two identical connexons assemble, or heterotypic, when two dissimilar connexons assemble between the two interacting cells [Dbouk H A et al., “Connexins: a myriad of functions extending beyond assembly of gap junction channels”, Cell Communication and Signaling, 2009, 7:4]. Due to the number of potential combinations of the approximately twenty available connexins, gap junctions composed of different connexin types can have different properties, for example, different permeability to molecules and ions. Therefore, the expression of multiple connexin proteins in a cell type is likely to confer different properties for GJIC in skin. Keratinocytes express temporally and spatially as many as 10 different connexins depending on their degree of differentiation. Not all connexins form compatible hemichannels which allow GJIC. The ability of connexins to form heteromeric hemichannels seems to be restricted to members of the same phylogenetic subgroup. Compatibility and incompatibility of connexins also increases the spectrum of intercellular communication, since it allows the generation of separate communication compartments for different molecules [Scott C A and Kelsell D P, “Key functions for gap junctions in skin and hearing”, Biochem J., 2011, Sep. 1; 438 (2):245-54]. Hemichannels are carried to the cell surface via vesicles transported through microtubules and finally, the hemichannels fuse to the plasma membrane to form gap junctions [Mee G et al., “Gap Junctions: Basic Structure and Function”, J. Investig. Dermatol., 2007, 127, 2516-2524]. The level of GJIC of a cell might be dynamically regulated at all levels of synthesis, assembly and degradation of connexins but also seems to depend on the function of other cell adhesion molecules, tight junction components and cytoskeletal elements [Dbouk H A et al., “Connexins: a myriad of functions extending beyond assembly of gap junction channels”, Cell Communication and Signaling, 2009, 7:4].
Gap Junction-mediated Intercellular Communication (GJIC) is important in different physiological processes including cell differentiation, proliferation, electrical transmission and inflammation [Scott C A, et al., “Connexins in epidermal homeostasis and skin disease”, Biochim. Biophys. Acta., 2012, August; 1818 (8): 1952-61]. The expression of some connexins, like Cx26 and Cx30, is upregulated during the initial response to wound healing, and Cx26 is upregulated in human hyperproliferative psoriatic lesions. Therefore, the upregulation of connexins, and particularly Cx26 and/or Cx30, might be a strategy for the treatment of skin inflammatory diseases and/or wound healing.
The decrease on cell communication is one of the mechanisms resulting in skin aging, i.e. the age-induced down-regulation of connexins is related with alterations in gap junctions [Dumont S et al., “Two new lipoaminoacids” Intl. J. Cosmet. Science, 2010, 32, 9-27]. The signs of decreased cellular communication are revealed on the skin's surface as fine lines, wrinkles, surface roughness, loss of elasticity, uneven skin tone, loss of firmness, or dryness. This age-related deterioration of the skin by down-regulation of connexins is particularly accelerated with the menopause. After menopause, many women suffer from a swift skin aging; skin becomes thinner with decreased collagen content, decreased elasticity, increased wrinkling and increased dryness. In postmenopausal women skin thickness decreases by 1.13% per postmenopausal year, with an associated decrease in collagen content (2% per post-menopausal year). The collagen content (types I and III) of skin is thought to decrease by as much as 30% in the first five years following the menopause [Thornton M J, “Estrogens and aging skin”, Dermatoendocrinol., 2013, 5(2):264-70]. Collagen is secreted mainly by fibroblasts with other extracellular matrix proteins that provide skin firmness and elasticity.
Therefore, an increase on the levels of connexin proteins would improve the cell communication and it would treat and delay the signs of skin aging such as wrinkles, irregular skin pigmentation, loss of elasticity, collagen, skin firmness, thickness and dryness.
Surprisingly, the applicant of this invention has found a ferment extract and an exopolysaccharide of bacterial origin that is an alternative to the previously mentioned problems.